Pre-Clinical Assessment of Bupivacaine-Loaded Poly(ester urea) Thin Films for Controlled Drug Release and Effective Pain Management After Surgery.

Abstract

Safe, effective pain management remains one of the biggest challenges following surgical procedures. Despite widespread recognition of this problem and advances in the mechanistic understanding of pain signaling, post-surgical pain is often undermanaged, with opioid use remaining the clinical standard. As an alternative to current oral, systemic treatments, a degradable bupivacaine-loaded poly(ester urea) (PEU) thin film has been developed to deliver bupivacaine directly to the site of injury over an extended duration. The dose and duration of bupivacaine delivery is controlled using polymer composition and bupivacaine concentration. Systemic bupivacaine concentrations are more than an order of magnitude lower when delivered locally versus intravenous injection. Tissue analysis showed that the majority of bupivacaine is deposited into subcutaneous tissue directly surrounding the implant. Bupivacaine concentration in soft tissue around the implant are 30-fold higher than plasma values, indicating that release from PEU implants remains localized. Bupivacaine-loaded PEU films are assessed into two established mouse models for diabetic neuropathic pain and post-surgical incisional pain. In each model, bupivacaine eluting PEU films effectively block pain for 3-5 days before returning to baseline levels without loss of motor function and without signs of neurotoxicity.